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Genetic Variability of HIV-1 Protease from Nigeria and Correlation with Protease Inhibitors Drug Resistance
Authors:Vicente  Ana Carolina P.  Agwale  Simon M.  Otsuki  Koko  Njouku  O.M.  Jelpe  D.  Idoko  J.A.  Caride  Elena  Brindeiro  Rodrigo M.  Tanuri  Amilcar
Affiliation:(1) Department of Genetics, Oswaldo Cruz Institute, Rio de Janeiro, Brazil;(2) Department of Zoology, Lab of Leishmaniasis and AIDS, University of Jos, Nigeria;(3) ISCC World Laboratory AIDS Research Center, Plateau Hospital, Jos, Nigeria;(4) Department of Medicine, Jos University Teaching Hospital, Jos, Nigeria
Abstract:In Nigeria, the most populous country in Africa, the characterization of HIV-1 strains has been limited. In this study we evaluated the genetic diversity of the protease coding region, one of the anti-retroviral therapy target, and investigated the presence of mutations related to resistance to HIV protease inhibitors. We analyzed samples collected during 1996 and all patients were anti-retroviral drug naimath¨ves. Ten samples were evaluated by sequencing of the protease gene. The majority, 80%, were classified as subtype A and the two others were unclassified-divergent strains, something in between A and G subtypes. The gag region from these outliners were sequenced and the phylogenetic analysis classified them as subtype G. The protease amino acid consensus sequence of the Nigerian subtype A are in complete agreement with the consensus A differing from the USA subtype B consensus in 10 positions (L10V, I13V, K14R, I15V, K20I, M36I, R41K, P63L, H69K and L89M).The secondary substitutions associated with protease inhibitor resistance were observed in all Nigerian sequences at the positions L10V, M36I and L89M. The majority of sequence variation was concentrated in the interval between aminoacids 70–90 where the protease substrate binding region is located.
Keywords:HIV-1  protease  subtype  anti-retroviral therapy  recombinant  mutation
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